There are 5.3 million Americans living with Alzheimer's disease (AD), the major neurodegenerative disease of aging, and the number of people affected by the disease is predicted to double within twenty years.
AD is a multifactorial disease characterized by Aβ deposition, tau hyperphosphorylation, oxidative stress, cholinergic deficits, progressive synaptic loss, and neurodegeneration. How all these typical characteristics of AD relate to each other is not clear. One of the earliest neuronal abnormalities in mild cognitive impairment (MCI) and AD is dysregulation of the cell cycle in postmitotic neurons, cells that are not normally cycling (Nagy et al., 1997; Vincent et al., 1997; Yang et al., 2001; Neve and McPhie, 2006; McShea et al., 2007; Bonda et al., 2010). Neuronal cell cycle regulatory failure presented by aberrant cell cycle entry (CCE) and often leading to cell death may be a significant component of AD pathogenesis. Accumulating evidence suggests that CCE in neurons may precede tau and amyloid pathology, and that there is a link between CCE and tau-hyperphosphorylation (Andorfer et al., 2005; Park et al., 2007; Jaworski et al., 2009). A number of studies indicates that almost all neurons that exhibit tau pathology are also positive for various markers of cell cycle (Busser et al., 1998; Keeney et al., 2012; Seward et al., 2013).
Despite significant progress in the field, medical science still has little to offer. Therefore, there is a critical need in new molecular targets, concepts, and approaches to treat this devastating disease.